Normal mature blood cells exhibit little proliferative activity and have a finite life span; the cells must, therefore, be replaced by a continuous process of recruitment and differentiation which is tightly regulated and accompanied by a loss of proliferative capacity. Leukemia is characterized by the accumulation of an abnormally large number of similar, usually immature, hemopoietic cells which appear to be in a state of differentiation encountered transiently during normal hemopoiesis. Leukemia is clearly the result of some unrestrained proliferative process but it is not clear if leukemic cells are able to respond to normal regulators of differentiation. These studies will focus on determining if induction in leukemic cells will reduce their leukemogenicity. The Abelson murine leukemia virus pseudotype of the lymphocytic leukemia virus of the regressing Friend virus (RF(A-MuLV)) induces a fatal non-thymic lymphoma in adult mice. The transformed hemopoietic cells can be phenotypically either lymphoid or monocytic. Cloned lines of both cell types will be systematically tested for the potential to differentiate using agents known to influence differentiation of murine hemopoietic cells. Differentiation will be monitored using markers for murine B-lymphocytes and granulocytic/monocytic cells. The effects of inducing differentiation on leukemogenicity and virus synthesis will then be tested.